.beta.-Adrenergic blockers were first reported to be useful for the treatment of glaucoma in 1967. Since then a vast number of .beta.-blockers have been investigated for ophthalmic use in treating eye disorders such as glaucoma, some of which, e.g. timolol, betaxolol, carteolol, metipranolol, befunolol and levobunolol, have reached clinical use as well. However, all of the compounds currently used for the treatment of humans are associated with a number of side effects, notably cardiovascular, respiratory, central nervous system and ocular side effects (see elg. J. Clin. Pharmacol. 29 (1989) 97).
This is also true of (S)-timolol, which is most commonly sold in its maleate salt form as a drug for the treatment of glaucoma. The (S)-timolol free base in itself is, however, a non-crystalline substance which is generally difficult to handle and to make into accurate dosage forms. Compositions containing, as the active antiglaucoma agent, only (S)-timolol maleate, which is a well-crystallizing substance, as well as their use, are described in the U.S. Pat. No. 4,195,085. In the said compositions timolol base itself without maleate anion is not employed. The presence of the maleate anion is a necessary component of the compositions, but as regards the activity of the preparation is completely superfluous and only constitutes an unnecessary load on the eye.
A further and well known disadvantage of ophthalmic solutions of timolol maleate salt is its sensitivity to light, which imposes strict requirements on the packaging and storage conditions for the maleate salt product, as well as on the carefulness of the patient in handling the product. Furthermore, the presence of the maleate anion may in some formulations have a negative influence on and even destroy the effect of ion-sensitive components.
Use of salt forms such as timolol maleate usually leads to the need of a large amount of additional ions which are delivered into the eye and may cause harmful effects.